In 66 breast cancer biopsies, the expression of the Ca 2+ -binding protein S100A4, E-cadherin, a-and b-catenin was examined by immunohistochemistry, and the results were related to clinical and pathological parameters. High levels of S100A4 were found to significantly correlate with histological grade (P=0.030) and loss of oestrogen receptor (P=0.046), but not to the time interval between surgery and development of distant metastasis (P=0.51) or to patient survival (P=0.89). Loss of Ecadherin expression, associated with altered cell -cell adhesion, showed a highly significant association to overall survival (P=0.020) and metastasis-free period (P=0.0052). In multivariate analysis, only lymph node involvement was a more significant predictor of patient demise. No association was found between expression of S100A4 and any single member of the cadherin -catenin complex, but a trend (P=0.053) towards reduced expression of one or several of these proteins and S100A4 immunoreactivity was observed. In conclusion, although our results suggest an association between S100A4 expression and an aggressive tumour phenotype, no relationship to overall survival was found. Deregulation of E-cadherin expression, however, was of high prognostic significance.

A large number of experimental studies have linked the S100A4 gene product to the metastatic phenotype of cancer cells and clinical evidence indicates a correlation between S100A4 expression and poor prognosis in several cancer types. The aim of the present study was to analyse the expression of the S100A4 protein in colorectal cancer. Paraffin-embedded samples from 277 colorectal cancer patients were immunostained with anti-S100A4 antibody. Cytoplasmic staining was observed in 178 of 277 samples (64%), whereas, unexpectedly, nuclear expression of S100A4 was found in 88 of 277 of the samples (32%). This novel finding was confirmed by western blot analysis of nuclear fractions isolated from frozen tumour tissue. Statistical analysis revealed a significant correlation between nuclear expression of S100A4 and tumour stage at diagnosis, while there was no such correlation between cytoplasmic staining and tumour stage. The nuclear localization of S100A4 in colorectal cancer and its relationship to tumour stage suggest that this protein may be involved in gene regulatory pathways of relevance to the metastatic phenotype of cancer cells.